Takeda Completes Enrollment of More Than 20,000 Children and Adolescents in Global Phase 3 Trial of Dengue Vaccine Candidate

  • Tetravalent Immunization against Dengue Efficacy Study (TIDES)
    trial evaluates the efficacy of two doses of vaccine candidate
    TAK-003, administered three months apart, to protect against all four
    strains of dengue virus, regardless of previous dengue exposure
  • Study includes children and adolescents ages 4 through 16 years in
    eight dengue-endemic countries across Latin America and Asia
  • Achieving enrollment demonstrates Takeda’s commitment to advancing
    global vaccine business and addressing unmet needs in dengue prevention

OSAKA, Japan–(BUSINESS WIRE)–Takeda Pharmaceutical Company Limited [TSE:
4502
], (“Takeda”) today announced that it has completed
enrollment of 20,100 children and adolescents ages 4 through 16 in
its global, pivotal Phase 3 Tetravalent Immunization against Dengue
Efficacy Study (TIDES) trial, a double-blind, randomized and
placebo-controlled study designed to evaluate the efficacy, safety and
immunogenicity of its live-attenuated tetravalent dengue vaccine
candidate (TAK-003).1 Takeda initiated the TIDES
trial, the largest vaccine clinical trial for Takeda to date, in
September 2016 and completed enrollment in less than seven months.1

“The successful enrollment of more than 20,000 children and adolescents
in this Phase 3 trial, across several continents, and on an ambitious
timeline, while maintaining a clear focus on quality and subject safety,
reflects Takeda’s prioritization of dengue and the substantial
capabilities of our global organization,” said Rajeev Venkayya, MD,
President of the Global Vaccine Business Unit at Takeda.

The study is taking place in eight dengue-endemic countries in Latin
America and Asia: Brazil, Colombia, Panama, Dominican Republic,
Nicaragua, Philippines, Thailand and Sri Lanka.1 While dengue
can affect people of all ages, it is a leading cause of serious illness
among children in some countries in Latin America and Asia.2
The enrollment of children and adolescents between the ages of 4 and 16
years underscores the significant burden of dengue disease across the
entire pediatric age range. Initial results of the TIDES trial are
expected in 2018.1

TIDES will build on previous studies which have assessed the
tolerability, safety and immunogenicity of the vaccine against all four
dengue serotypes in multiple age groups to determine whether the vaccine
helps prevent symptomatic dengue.3,4,5,6,7 In Phase 1 and
Phase 2 studies, Takeda’s vaccine candidate induced neutralizing
antibody responses against all four dengue virus serotypes across age
groups and in both seropositive and seronegative individuals with no
observed safety concerns.3,4,5,6,7 Interim results of one
Phase 2 study (DEN-203) showed the vaccine to be generally safe and well
tolerated.3,5 Results also showed that adults vaccinated with
two doses had a sustained immune response against all four serotypes of
the dengue virus, even after two years.5 Interim results of
another Phase 2 study (DEN-204) showed an acceptable safety profile in
endemic pediatric populations, as well as antibody responses against the
four dengue serotypes in dengue seropositive and seronegative
participants, with a sustained immune response through 180 days.6,7

“This enrollment milestone demonstrates our commitment to a thorough
evaluation of the safety and efficacy of our vaccine candidates and,
subject to licensure, ensuring that they are available to all
populations at risk. It follows Takeda’s recent decision to invest
more than 100 million euros to build a new plant for the manufacturing
of TAK-003
,” said Venkayya. “Beyond dengue, Takeda is pursuing a
number of vaccine programs to address high-priority infectious diseases
including our Zika program funded
by the U.S. Government’s Biomedical Advanced Research and Development
Authority (BARDA)
and our polio program supported
by the Bill & Melinda Gates Foundation
.”

About the Phase 3 TIDES Study1

TIDES is investigating the efficacy, safety and immunogenicity of two
doses of TAK-003 administered three months apart. TIDES participants
were randomized to receive a two-dose regimen of either TAK-003 or
placebo by subcutaneous injection at Day 1 and Day 90. A subset of these
participants was randomly selected and stratified by region and age to
be included in the safety and immunogenicity subsets. Efficacy
assessments will take place once 120 cases of virologically confirmed
dengue have accrued and after a minimum subject follow-up period of 12
months, post second vaccination.

The primary outcome measure is vaccine protection against
virologically-confirmed dengue of any severity, caused by any of the
four dengue virus serotypes, regardless of whether a subject has been
previously exposed to dengue. Secondary endpoints include vaccine
efficacy in preventing dengue induced by each dengue serotype, vaccine
efficacy in preventing hospitalization due to dengue induced by any
serotype, vaccine efficacy in preventing severe dengue induced by any
serotype, frequency and severity of Adverse Events (AEs) or
Serious Adverse Events (SAEs), and seropositivity rate and geometric
mean titers (GMTs) of neutralizing antibodies in the immunogenicity
subset.

About TAK-003

Takeda’s tetravalent dengue vaccine candidate (TAK-003) is based on a
live-attenuated dengue serotype 2 virus (DENV-2), which provides the
genetic ‘backbone’ for all four vaccine viruses.8 Phase 1 and
2 data have supported progression into Phase 3 study, suggesting that
TAK-003 is safe and well-tolerated in children and adolescents (no
vaccine-related SAEs occurred and reactogenicity was limited) and
induced immunogenicity against all four dengue serotypes, even in
seronegative participants.4,5,6,7

About Dengue

Dengue is the fastest spreading mosquito-borne viral disease.2
Dengue is spread by Aedes aegypti and Aedes albopictus mosquitoes
and is caused by four dengue virus serotypes, each of which can cause
dengue fever or severe dengue.9,10 The serotypes vary across
different geographies, countries, regions, seasons and over time.11,12

Dengue outbreaks are observed in tropical and sub-tropical areas and
have recently caused outbreaks in parts of mainland U.S. and Europe.9,13,14
Forty percent of the world now lives under the threat of dengue, which
is responsible for approximately 390 million infections and 20,000
deaths globally each year.9,10 Dengue virus can infect people
of all ages and is a leading cause of serious illness among children in
some countries in Latin America and Asia.2

Takeda’s Commitment to Vaccines

Vaccines prevent more than two million deaths each year and have
transformed global public health.15 For 70 years, Takeda has
supplied vaccines to protect the health of people in Japan. Today,
Takeda’s global vaccine business is applying innovation to tackle some
of the world’s most challenging infectious diseases, such as dengue,
Zika, norovirus and polio. Our team brings an outstanding track record
and a wealth of knowledge in vaccine development, manufacturing and
global access to advance a pipeline of vaccines to address some of the
world’s most pressing public health needs.

About Takeda Pharmaceutical Company Limited

Takeda Pharmaceutical Company Limited (TSE:
4502
) is a global, R&D-driven pharmaceutical company committed to
bringing better health and a brighter future to patients by translating
science into life-changing medicines. Takeda focuses its research
efforts on oncology, gastroenterology and central nervous system
therapeutic areas. It also has specific development programs in
specialty cardiovascular diseases as well as late-stage candidates for
vaccines. Takeda conducts R&D both internally and with partners to stay
at the leading edge of innovation. New innovative products, especially
in oncology and gastroenterology, as well as its presence in emerging
markets, fuel the growth of Takeda. More than 30,000 Takeda employees
are committed to improving quality of life for patients, working with
our partners in health care in more than 70 countries. For more
information, visit http://www.takeda.com/news.

1 ClinicalTrials.gov. Efficacy,
Safety and Immunogenicity of Takeda’s Tetravalent Dengue Vaccine (TDV)
in Healthy Children (TIDES)
. 2016. Retrieved March 2017.

2 World Health Organization. Vector-borne
Diseases: Dengue
. 2015. Retrieved January 2017.

3 Osorio, J.E., et al.
Development of a Recombinant, Chimeric Tetravalent Dengue Vaccine
Candidate
. Vaccine. 2015. Retrieved March 2017.

4 Osorio, J.E., et al. Safety
and immunogenicity of a recombinant live attenuated tetravalent dengue
vaccine (DENVax) in flavivirus-naive healthy adults in Colombia: a
randomised, placebo-controlled, phase 1 study
. The Lancet
Infectious Diseases
. 2014. Retrieved May 2016.

5 Wallace, D. Persistence of neutralizing antibodies one year
after two doses of a candidate recombinant tetravalent dengue vaccine in
subjects aged from 1.5 to 45 years. Presented at 6th Annual Meeting,
American Society of Tropical Medicine and Hygiene. 2015.

6 Saez-Llorens X., et al. Phase II, double-blind, controlled
trial to assess the safety and immunogenicity of different schedules of
Takeda’s Tetravalent Dengue Vaccine Candidate (TDV) in healthy subjects
aged between 2 and <18 years and living in dengue endemic countries in
Asia and Latin America. Presented at 5th Pan-American Dengue Research
Network Meeting. 2016.

7 Sáez-Llorens, X., et al. Safety
and immunogenicity of one versus two doses of Takeda’s tetravalent
dengue vaccine: Interim results of a long-term phase 2, randomized,
placebo-controlled pediatric trial in Asia and Latin America
. The
Lancet Infectious Diseases
. 2017. Retrieved March 2017.

8 Huang, C. Y.-H., et al. Genetic
and Phenotypic Characterization of Manufacturing Seeds for Tetravalent
Dengue Vaccine (DENVax)
. PLoS Neglected Tropical Diseases.
2013. Retrieved May 2016.

9 World Health Organization. Dengue
and Severe Dengue
. 2016. Retrieved January 2017.

10 Centers for Disease Control and Prevention. Clinical
Guidance Dengue Virus.
2014. Retrieved January 2017.

11 Bravo, L., et al. Epidemiology
of Dengue Disease in the Philippines (2000-2011): A Systematic
Literature Review
. PLoS Neglected Tropical Diseases. 2014.
Retrieved January 2017.

12 Guzman, M.G., et al. Dengue:
a continuing global threat
. Nature reviews Microbiology.
2010. Retrieved May 2016.

13 Knowlton, K., et al. NRDC Issue Paper: Mosquito-Borne
Dengue Fever Threat Spreading in the Americas
. 2009. Retrieved May
2016.

14 Chan E., et al. Using
Web Search Query Data to Monitor Dengue Epidemics: A New Model for
Neglected Tropical Disease Surveillance
. PLoS Neglected Tropical
Diseases
. 2011. Retrieved January 2017.

15 UNICEF. Immunization
Facts and Figures
. 2013. Retrieved January 2017.

Contacts

Takeda Pharmaceutical Company Limited
For media outside of Japan:
Elissa
J. Johnsen
TEL: + 1 224-554-3185
elissa.johnsen@takeda.com
or
For
Japanese media:
Tsuyoshi Tada
TEL: +81-3-3278-2417
tsuyoshi.tada@takeda.com